Spitzoid melanoma with histopathological features of ALK gene rearrangement exhibiting ALK copy number gain: a novel mechanism of ALK activation in spitzoid neoplasia. (12th September 2018)

• Record Type: Journal Article
• Authors: Farah, M.; Nagarajan, P.; Curry, J.L.; Tang, Z.; Kim, T.‐B.; Aung, P.P.; Torres‐Cabala, C.A.; Eterovic, A.K.; Wargo, J.A.; Prieto, V.G.; Tetzlaff, M.T.
• Is Part Of: British journal of dermatology. Volume 180:Number 2(2019)
• Page Start: 404
• Page End: 408
• Publication Date: 2018-09-12
• Subjects: Dermatology -- Periodicals; Skin -- Diseases -- Periodicals; 616.5
• DOI: 10.1111/bjd.16881
• Languages: English
• ISSNs: 0007-0963

Abstract

Summary: Spitzoid neoplasms pose diagnostic difficulties because their morphology is not consistently predictive of their biological potential. Recent advances in the molecular characterization of these tumours provides a framework by which they can now begin to be categorized. In particular, spitzoid lesions with ALK rearrangement have been specifically associated with a characteristic plexiform growth pattern of intersecting fascicles of amelanotic spindled melanocytes. We report the case of an 87‐year‐old man with a 3‐cm nodule on his mid‐upper back comprised of an intradermal proliferation of fusiform amelanotic melanocytes arranged in intersecting fascicles with occasional peritumoral clefts. Immunohistochemical studies demonstrated diffuse, strong expression of SOX10 and S100 by the tumour cells and diffuse, weak‐to‐moderate cytoplasmic positivity for anaplastic lymphoma kinase (ALK), suggestive of ALK rearrangement. Fluorescence in situ hybridization revealed no ALK rearrangements but instead revealed at least three intact ALK signals in 36% of the tumour cells, confirming ALK copy number gain. To our knowledge, this is the first reported case of a plexiform spitzoid neoplasm exhibiting ALK copy number gain instead of ALK rearrangement. This case suggests that ALK copy number gain is a novel mechanism of ALK activation but with the same characteristic histopathological growth pattern seen among ALK‐rearranged spitzoid neoplasms. Abstract : What's already known about this topic? Spitzoid neoplasms frequently pose diagnostic difficulty in distinguishing the relatively more common indolent lesions from the rare metastasizing spitzoid melanoma. Recent studies have elaborated a molecular genetic framework by which to categorize these tumours, and it is now known that certain discrete alterations correlate with specific clinical and/or pathological features. Spitzoid lesions with ALK gene rearrangement exhibit a distinctive plexiform pattern of growth with intersecting fascicles of amelanotic spindled melanocytes. What does this study add? We report the first case of a plexiform spitzoid neoplasm exhibiting ALK copy number gain instead of ALK rearrangement. ALK copy number gain represents a novel mechanism of ALK activation among spitzoid tumours and is associated with the same characteristic histopathological growth pattern seen among ALK‐rearranged spitzoid neoplasms. Linked Comment: Chan. Br J Dermatol 2019;180 :262 . Plain language summary available online